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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which results in tumor...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
Bone Remodeling and Repair01:31

Bone Remodeling and Repair

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during bone...
Bone Remodeling01:40

Bone Remodeling

Bone remodeling is a continuous and balanced process of bone resorption by osteoclasts and bone formation by osteoblasts. In adults, it helps maintain bone mass and calcium homeostasis. While mechanical stress can stimulate turnover as part of the normal maintenance and reparative process, several hormones also regulate bone remodeling.

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Related Experiment Video

Updated: Jun 10, 2026

Simple Establishment of a Vascularized Osteogenic Bone Marrow Niche Using Pre-Cast Poly(ethylene Glycol) (PEG) Hydrogels in an Imaging Microplate
10:32

Simple Establishment of a Vascularized Osteogenic Bone Marrow Niche Using Pre-Cast Poly(ethylene Glycol) (PEG) Hydrogels in an Imaging Microplate

Published on: May 19, 2023

WISP-1/CCN4 regulates osteogenesis by enhancing BMP-2 activity.

Mitsuaki Ono1, Colette A Inkson, Tina M Kilts

  • 1Craniofacial and Skeletal Diseases Branch, National Institutes of Craniofacial and Dental Research, National Institutes of Health, Bethesda, MD 20892, USA.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|August 5, 2010
PubMed
Summary

Wnt-induced secreted protein 1 (WISP-1) enhances bone formation by boosting BMP-2 signaling. This protein interacts with BMP-2 and integrin α(5)β(1), promoting osteogenesis in bone marrow stromal cells and increasing bone density in vivo.

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Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Related Experiment Videos

Last Updated: Jun 10, 2026

Simple Establishment of a Vascularized Osteogenic Bone Marrow Niche Using Pre-Cast Poly(ethylene Glycol) (PEG) Hydrogels in an Imaging Microplate
10:32

Simple Establishment of a Vascularized Osteogenic Bone Marrow Niche Using Pre-Cast Poly(ethylene Glycol) (PEG) Hydrogels in an Imaging Microplate

Published on: May 19, 2023

Stimulation of Notch Signaling in Mouse Osteoclast Precursors
08:01

Stimulation of Notch Signaling in Mouse Osteoclast Precursors

Published on: February 28, 2017

Area of Science:

  • Cell Biology
  • Biochemistry
  • Orthopedics

Background:

  • Wnt-induced secreted protein 1 (WISP-1/CCN4) is a CCN family member highly expressed in skeletal tissue.
  • Osteoprogenitor cells are crucial for bone formation, and their differentiation is regulated by signaling pathways.

Purpose of the Study:

  • To determine the function of WISP-1 in osteogenesis.
  • To elucidate the mechanism by which WISP-1 influences bone formation, particularly its interaction with bone morphogenetic protein 2 (BMP-2).

Main Methods:

  • Overexpression of WISP-1 using adenovirus (adWISP-1) and BMP-2 (adBMP-2) in bone marrow stromal cells (BMSCs).
  • In vivo ectopic osteogenesis assays and lentiviral shRNA knockdown of WISP-1.
  • Immunoprecipitation, Western blot, and antibody-blocking experiments to analyze protein interactions and signaling pathways.
  • Analysis of integrin expression and function.

Main Results:

  • WISP-1 overexpression enhanced BMP-2-induced osteogenic differentiation of BMSCs by stimulating Smad-1/5/8 phosphorylation.
  • WISP-1 directly bound to BMP-2 and increased its binding to BMSCs.
  • WISP-1 upregulated α(5)-integrin expression and bound to it, mediating BMP-2 enhancement.
  • WISP-1 knockdown reduced bone formation in vivo and BMP-2 responsiveness.
  • Transgenic mice overexpressing WISP-1 showed increased bone mineral density and improved bone structure.

Conclusions:

  • WISP-1 positively influences osteogenesis by enhancing BMP-2 signaling, potentially through binding to integrin α(5)β(1).
  • WISP-1 plays a significant role in bone cell differentiation and function, both in vitro and in vivo.
  • WISP-1 represents a potential therapeutic target for promoting bone formation and treating bone-related disorders.